Báo cáo ca lâm sàng: Hội chứng tự miễn insulin do methimazole gây hạ đường huyết ở một phụ nữ trẻ mắc bệnh Graves

Abstract

Background: Insulin autoimmune syndrome (IAS, Hirata disease) is a rare cause of hyperinsulinemic hypoglycemia caused by autoantibodies against endogenous insulin in patients with no prior exposure to exogenous insulin. It is strongly associated with sulfhydryl-containing drugs such as methimazole and with HLA-DRB1*04 alleles, and is reported predominantly in East Asian populations. According to our review, no similar cases have been reported in Vietnam. Case presentation: A 34-year-old Vietnamese woman with newly diagnosed Graves’ disease was treated with thiamazole (methimazole) 15 mg/day. Approximately three months after starting the drug, she developed recurrent episodes of autonomic and neuroglycopenic hypoglycemia occurring predominantly 3 - 4 hours postprandially, which persisted despite discontinuation of all medications. On admission, fasting venous glucose was 3.55mmol/L with a markedly elevated serum insulin (1000µU/mL). During a symptomatic episode (glucose 3.34mmol/L), insulin was 4652.9µU/mL and C-peptide 11.34ng/mL, giving a disproportionately high insulin-to-C-peptide ratio (8.9; when converted to the same unit of measurement; normal < 1, with insulin concentration is expressed in µIU/mL and C-peptide concentration in ng/mL), with strongly positive insulin autoantibodies (> 175AU/mL). Quantitative tests for Insulin, C-peptide, and IAA antibodies are all performed using the chemiluminescence method. HLA typing showed DRB1*0403, and pancreatic ultrasound imaging showed no pancreatic tumour. Methimazole-induced IAS was diagnosed. Discontinuation of the offending drug together with small frequent meals, acarbose and oral glucocorticoids led to resolution of hypoglycemia within one week. Radioactive iodine (I-131) was planned as definitive treatment for Graves’ disease, but the patient was lost to follow-up due to the significant improvement in clinical symptoms of hypoglycemia, which rarely occur. Conclusion: IAS should be considered in patients with Graves’ disease who develop recurrent hyperinsulinemic hypoglycemia during methimazole therapy, particularly when the insulin-to-C-peptide ratio is disproportionately elevated and insulin autoantibodies are positive. Early recognition avoids unnecessary investigation for insulinoma, allows prompt withdrawal of the offending drug and supportive treatment, and is generally associated with a good prognosis.